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A Little TiPED History: Putting the Protocol Together.

A representative diagram of the draft screening protocol unveiled at the meeting. The protocol is designed in a tiered approach, with rapid and cost effective screens conducted in the early phases and more extensive testing toward the end. (Slide courtesy of Pete Myers)

NIEHS/NTP scientists joined forces with leaders in the field of green chemistry in what may turn out to be a groundbreaking meeting, “Green Chemistry and Environmental Health Sciences — Designing Endocrine Disruption Out of the Next Generation of Materials,” held March 21-23 in Sausalito, Calif.

The challenges facing scientists trying to design such new materials are daunting. Say a chemist has developed a compound that he or she believes could be a replacement for bisphenol A (BPA). How will the scientist determine if the molecule is safer to human health and the environment? What testing will need to be done and what will guide scientists through this process?

The goals of the meeting in Sausalito were ambitious — to develop a consensus statement on the principles that guide the science needed to assess risks of potential endocrine disruptors, and to develop a reliable and rational testing protocol to aid chemists as they develop and bring the next generation of chemicals into the marketplace.

The intersection of green chemistry and environmental health science

Karen O’Brien, Ph.D., from Advancing Green Chemistry (AGC) and Pete Myers, Ph.D., of Environmental Health Sciences (EHS), welcomed participants to the event, which brought together an equal mix of biologists and chemists. Representatives from NIEHS and NTP included Division of Extramural Research and Training (DERT) program administrator Jerry Heindel, Ph.D., and Kristina Thayer, Ph.D., director of the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR).

Following a social ice-breaking exercise on the evening of March 21, the first full day of the meeting opened with presentations from Terry Collins, Ph.D., the Teresa Heinz Professor of Green Chemistry at Carnegie Mellon University, and John Warner, Ph.D., president and founder of the Warner Babcock Institute for Green Chemistry.

Both Collins and Warner stressed the need for fundamental changes in the way that scientists design new chemicals and the process of bringing them into the marketplace. “We must also pay close attention to the environmental impact and the effects on human health posed by these chemicals, and for those reasons chemists need to work hand-in-hand with biologists,” said Warner. He also stressed that chemists generally have no background in toxicology, but that they need to be able to test the chemicals being developed for endocrine activity and to do it early on in the product development process.

Designing a chemical screening protocol

The remainder of the day was divided into discussion sessions covering each phase of a newly developed screening model, designed by a science advisory board formed by meeting organizers that met monthly, via teleconference, for six months prior to the workshop. The protocol is geared towards identifying a wide-range of endocrine-active chemicals, such as atrazine, BPA, brominated flame retardants, organotins, perchlorates, and phthalates. The Board conducted interviews with scientists with expertise in specific areas of toxicology, endocrine disruption, and assay development.

The testing paradigm proposed involves a five-tiered approach, starting with the fastest and cheapest assays and working through more specialized tests to determine whether a new chemical has endocrine disrupting characteristics. The initial two phases rely on predictive computer modeling and high-throughput screening to quickly weed out problem chemicals. These tests are followed by more specific in vitro cell-based screening assays with a mind to refining, reducing, and replacing animal testing as much as possible.

The final two phases involve use of fish, amphibian, and mammalian in vivo modeling systems. Overall, the protocol is intended to help green chemists establish a high degree of confidence that the replacements they are developing are unlikely to be harmful to humans or the environment.

The next steps

The meeting wrapped up with discussion on how to proceed with development of the testing protocol as well as plans for implementation. The advisory board plans to use input from the meeting to develop and publish a white paper outlining guidelines that chemists can use to assess the quality of protocols and tests used to assess endocrine disruption.

(Thaddeus Schug, Ph.D., is a postdoctoral research fellow currently on detail as a program analyst in the NIEHS Division of Extramural Research and Training. He was part of the NIEHS/NTP delegation and a presenter at the meeting.)

Left to right, Collins, Heindel, and Warner mix ingredients for a batch of salmon tartare. The cooking exercise was used as an ice-breaking event to demonstrate how environmental health scientists and chemists can work together to solve complex issues. (Photo courtesy of Pete Myers)

Left to right, Bruce Blumberg, Ph.D., Thayer, and Andreas Kortenkamp, Ph.D., served as panel members for a discussion on in vitro screening assays. (Photo courtesy of Pete Myers)

A group photo of the meeting attendees. The meeting was held at the Cavallo Point Lodge, which sits adjacent to the Golden Gate Bridge. (Photo courtesy of Pete Myers)

NIEHS grantees Andrea Gore, Ph.D., left, and Frederick vom Saal, Ph.D., were among panel members for the discussion on in vivoassays. Both Gore and vom Saal are members of the project’s scientific advisory board. (Photo courtesy of Pete Myers)

Emerging Environmental Health Science in Green Chemistry

NIEHS Senior Advisor for Public Health John Balbus, M.D., attended the inaugural symposium March 24 for the new University of California, Berkeley Center for Green Chemistry, entitled “Green Chemistry: Collaborative Approaches and New Solutions.” Balbus’ talk, “Incorporating Emerging Environmental Health Science in Green Chemistry,” outlined some of the challenges of applying 21st century science to protect public health.

How do we harness the potential of unlocking the genome?

Can we more accurately predict which chemicals are likely to cause harm?

How do we implement our understanding of susceptibility and non-chemical stressors to enhance human health?

How can we better incorporate new methods and technologies into science policy?

Balbus proposed that the newly developed Tox21 (http://ntp.niehs.nih.gov/index.cfm?objectid=06002ADB-F1F6-975E-73B25B4E3F2A41CB), an interagency high throughput screening initiative, is aiming to meet many of these challenges and could be a valuable tool for green chemists. Demonstrating its utility in screening chemicals for disruptions in insulin signaling, Balbus concluded, “Advancements in programs such as Tox21 will eventually allow us to accurately predict how chemicals will impact human health before they are brought into the marketplace.”